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Cambridge Cardiovascular

 

Research

Developmental Origins of Heart Disease

We work with small and large animal models to investigate the effects of adverse pregnancy on the development of the heart and circulation and in programming cardiovascular disease in the adult offspring.  We are able to study the cardiovascular system using an integrative approach at the in vivo, isolated organ, cellular and molecular levels. 

We have a particular interest on the effects of hypoxia during embryonic and fetal development and its long-term consequences for cardiovascular risk in the adult offspring.  In larger animals, such as sheep, we are experienced fetal cardiac surgeons and we can surgically prepare the pregnant ewe and fetus for long-term cardiovascular recording with blood pressure catheters and Transonic flow probes around vessels of interest, like the uterine, umbilical artery, fetal carotid and fetal femoral artery.

In sheep, rats, mice and chickens we combine our in vivo surgical expertise with echocardiography, isolated Langendorff and Working Heart preparations as well in vitro wire myography to determine changes in the reactivity of isolated blood vessels.

Our research group has pioneered the role of prenatal hypoxia and oxygen species in fetal physiology and in programming cardiovascular disease in later life.  Our landmark discoveries are, showing that the circulatory response that protects the fetal brain during hypoxia is triggered exclusively by the carotid body, establishing that hypoxia restricts fetal growth and identifying resistance against this in Andeans, elucidating that hypoxic pregnancy accelerates cardiovascular ageing in the offspring; effects prevented by maternal antioxidant treatment.  We have developed wireless technology to record materno-fetal continuous cardiovascular data from sheep undergoing hypoxic pregnancy; an advance opening the scientific possibilities of fetal physiological research.

Publications

Key publications: 

Please follow link for full list of publications on PubMed

  1. Cetin I, Taricco E, Mandò C, Radaelli T, Boito S, Nuzzo AM, Giussani DA. Fetal Oxygen and Glucose Consumption in Human Pregnancy Complicated by Fetal Growth Restriction. Hypertension. 2020 Mar;75(3):748-754.
  2. Frasch MG, Herry CL, Niu Y, Giussani DA.  First evidence that intrinsic fetal heart rate variability exists and is affected by hypoxic pregnancy. J Physiol. 2020 Jan;598(2):249-263.
  3. Jellyman JK, Fletcher AJW, Fowden AL, Giussani DA.Glucocorticoid Maturation of Fetal Cardiovascular Function. Trends Mol Med. 2020 Feb;26(2):170-184.
  4. Brain KL, Allison BJ, Niu Y, Cross CM, Itani N, Kane AD, Herrera EA, Skeffington KL, Botting KJ,Giussani DA. Intervention against hypertension in the next generation programmed by developmental hypoxia. PLoS Biol. 2019 Jan 22;17(1): e2006552.
  5. Niu Y, Kane AD, Lusby CM, Allison BJ, Chua YY, Kaandorp JJ, Nevin-Dolan R, Ashmore TJ, Blackmore HL, Derks JB, Ozanne SE, Giussani DA. Maternal Allopurinol Prevents Cardiac Dysfunction in Adult Male Offspring Programmed by Chronic Hypoxia During Pregnancy. Hypertension. 2018 Oct;72(4):971-978.
  6. Giussani, D.A., Camm, E.J., Niu, Y., Richter, H.G., Blanco, C.E., Gottschalk, R., Blake, E.Z., Horder, K.A., Thakor, A.S., Hansell, J.A., Kane, A.D., Wooding, F.B.P., Cross C.M. & Herrera. E.A. (2012).  Developmental programming of cardiovascular dysfunction by prenatal hypoxia and oxidative stress.  PLoS ONE 7(2), e31017. News piece written in Science Magazine about this work entitled: Embryos Starved of Oxygen May Be 'Programmed' for Heart Disease by Jean Friedman-Rudovsky on 13 February 2012. http://news.sciencemag.org/sciencenow/2012/02/embryos-starved-of-oxygen-may-be.html
  7. Giussani, D.A. (2011).  The vulnerable developing brain. Proc Natl Acad   Sci USA. 108(7), 2641-2.
  8. Thakor, A.S. & Giussani, D.A. (2005).  The role of nitric oxide in mediating in vivo vascular responses to calcitonin gene related peptide in essential and peripheral circulations in the fetus. Circulation 112(16):2510-6.
  9. Gardner, D.S., Fowden, A.L. & Giussani, D.A. (2002). Adverse intrauterine conditions diminish the fetal defense to acute hypoxia by increasing nitric oxide activity. Circulation 106: 2278-2283.
  10. Gardner DS, Giussani DA. Enhanced umbilical blood flow during acute hypoxemia after chronic umbilical cord compression: a role for nitric oxide. Circulation. 2003;108(3):331-5.

 

Professor of Developmental Cardiovascular Physiology and Medicine
Director of Perinatal Physiology Research Group at The Barcroft Centre
Professor Dino A Giussani

Affiliations

Classifications: 
Person keywords: 
development
endothelial function
molecular biology
oxidative stress
cardiovascular therapy
pulmonary hypertension
echocardiography
hypoxia
epigenetics
hypertension
arterial stiffness
myocardial ischaemia
cardiovascular physiology
heart development
cardiometabolic disease
haemodynamic monitoring